The effect of Wnt10b overexpression on adipose tissue development has been reported. However, the impact of Wnt10b knockdown on the function of brown adipose tissue (BAT) is yet largely unknown. Here, we used the CRISPR/Cas9 technique to generate Wnt10b-knockdown (Wnt10b^+/−) mice. We compared the development and thermogenic gene expression of interscapular BAT (iBAT) between Wnt10b^+/− and Wnt10b^+/+ mice under a chow diet, high-fat diet (HFD), and cold exposure conditions. Moreover, the effect of Wnt10b knockdown on brown adipocyte function was tested via in vitro experiments. Results indicated that Wnt10b knockdown decreased the iBAT mass and the brown adipocyte size and enhanced thermogenic gene expression, including UCP1, under chow diet conditions. In addition, Wnt10b^+/− mice appeared to be able to maintain their body temperature better than the control in a cold environment, accompanied by higher UCP1 protein expression. Intriguingly, even under HFD conditions, Wnt10b^+/− mice still showed higher UCP1 expression, which was associated with an alleviated obesity phenotype. In vitro studies further evidenced the Wnt10b knockdown stimulation of UCP1 expression and suppression of the adipogenic program. This study indicates that Wnt10b knockdown enhances UCP1 expression and inhibits the adipogenic differentiation of brown adipocytes, providing a novel option for therapeutic interventions in adiposity.

中文翻译：

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Wnt10b 敲低促进小鼠棕色脂肪组织中 UCP1 的表达

Wnt10b过度表达对脂肪组织发育的影响已有报道。然而， Wnt10b敲低对棕色脂肪组织 (BAT) 功能的影响尚不清楚。在这里，我们使用 CRISPR/Cas9 技术来生成Wnt10b敲低 ( Wnt10b ^+/- ) 小鼠。我们比较了Wnt10b ^+/-和Wnt10b ^+/+小鼠在食物饮食、高脂饮食 (HFD) 和寒冷暴露条件下的发育和肩胛间 BAT (iBAT) 的产热基因表达。此外，通过体外实验测试了Wnt10b敲低对棕色脂肪细胞功能的影响。结果表明，在饲料条件下，Wnt10b敲低降低了 iBAT 质量和棕色脂肪细胞大小，并增强了产热基因表达，包括UCP1 。此外，Wnt10b ^+/-小鼠似乎能够在寒冷环境中比对照小鼠更好地维持体温，同时 UCP1 蛋白表达更高。有趣的是，即使在 HFD 条件下，Wnt10b ^+/-小鼠仍表现出较高的 UCP1 表达，这与肥胖表型减轻有关。体外研究进一步证明Wnt10b敲低可刺激 UCP1 表达并抑制脂肪形成程序。这项研究表明Wnt10b敲低增强了UCP1表达并抑制棕色脂肪细胞的成脂分化，为肥胖症的治疗干预提供了新的选择。